US2719150A - Process for the manufacture of octahydroisoquinoline derivatives and intermediates therein - Google Patents
Process for the manufacture of octahydroisoquinoline derivatives and intermediates therein Download PDFInfo
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- US2719150A US2719150A US256623A US25662351A US2719150A US 2719150 A US2719150 A US 2719150A US 256623 A US256623 A US 256623A US 25662351 A US25662351 A US 25662351A US 2719150 A US2719150 A US 2719150A
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- parts
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- methyl
- alkyl
- octahydroisoquinoline
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- LRGZZEOWQURWFK-UHFFFAOYSA-N 1,2,3,4,4a,5,6,7-octahydroisoquinoline Chemical class C1NCCC2CCCC=C21 LRGZZEOWQURWFK-UHFFFAOYSA-N 0.000 title description 4
- 238000000034 method Methods 0.000 title description 4
- 239000000543 intermediate Substances 0.000 title description 3
- 238000004519 manufacturing process Methods 0.000 title description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- -1 alkyl amides Chemical class 0.000 description 11
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- 229910052739 hydrogen Inorganic materials 0.000 description 4
- 239000001257 hydrogen Substances 0.000 description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 4
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- FHEPZBIUHGLJMP-UHFFFAOYSA-N cyclohexene Chemical compound [CH]1CCCC=C1 FHEPZBIUHGLJMP-UHFFFAOYSA-N 0.000 description 3
- MFYSUUPKMDJYPF-UHFFFAOYSA-N 2-[(4-methyl-2-nitrophenyl)diazenyl]-3-oxo-n-phenylbutanamide Chemical compound C=1C=CC=CC=1NC(=O)C(C(=O)C)N=NC1=CC=C(C)C=C1[N+]([O-])=O MFYSUUPKMDJYPF-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 239000007868 Raney catalyst Substances 0.000 description 2
- NPXOKRUENSOPAO-UHFFFAOYSA-N Raney nickel Chemical compound [Al].[Ni] NPXOKRUENSOPAO-UHFFFAOYSA-N 0.000 description 2
- 229910000564 Raney nickel Inorganic materials 0.000 description 2
- 239000007864 aqueous solution Substances 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- WUAXWQRULBZETB-UHFFFAOYSA-N homoveratric acid Chemical compound COC1=CC=C(CC(O)=O)C=C1OC WUAXWQRULBZETB-UHFFFAOYSA-N 0.000 description 2
- 150000002431 hydrogen Chemical class 0.000 description 2
- 238000005984 hydrogenation reaction Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- TZIHFWKZFHZASV-UHFFFAOYSA-N methyl formate Chemical compound COC=O TZIHFWKZFHZASV-UHFFFAOYSA-N 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- YBYCJQQRZPXLHU-UHFFFAOYSA-N 1,2,3,4,5,6,7,8-octahydroisoquinoline Chemical compound C1CNCC2=C1CCCC2 YBYCJQQRZPXLHU-UHFFFAOYSA-N 0.000 description 1
- ZYYDNMRUDMCOHG-UHFFFAOYSA-N 1-benzyl-2-methyl-3,4,5,6,7,8-hexahydro-1h-isoquinoline Chemical compound CN1CCC(CCCC2)=C2C1CC1=CC=CC=C1 ZYYDNMRUDMCOHG-UHFFFAOYSA-N 0.000 description 1
- CXJOONIFSVSFAD-UHFFFAOYSA-N 2-(4-methoxyphenyl)acetyl chloride Chemical compound COC1=CC=C(CC(Cl)=O)C=C1 CXJOONIFSVSFAD-UHFFFAOYSA-N 0.000 description 1
- VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 description 1
- SDRVOPJWDGNEDE-UHFFFAOYSA-N C1(=CCCCC1)CCN(C(CC1=CC=C(C=C1)OC)=O)C Chemical compound C1(=CCCCC1)CCN(C(CC1=CC=C(C=C1)OC)=O)C SDRVOPJWDGNEDE-UHFFFAOYSA-N 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 238000007126 N-alkylation reaction Methods 0.000 description 1
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 1
- 230000010933 acylation Effects 0.000 description 1
- 238000005917 acylation reaction Methods 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cis-cyclohexene Natural products C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 description 1
- 238000004040 coloring Methods 0.000 description 1
- 239000007859 condensation product Substances 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- AWJUIBRHMBBTKR-UHFFFAOYSA-N iso-quinoline Natural products C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- 239000000155 melt Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910001392 phosphorus oxide Inorganic materials 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- LFGREXWGYUGZLY-UHFFFAOYSA-N phosphoryl Chemical class [P]=O LFGREXWGYUGZLY-UHFFFAOYSA-N 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/02—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines
- C07D217/04—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with only hydrogen atoms or radicals containing only carbon and hydrogen atoms, directly attached to carbon atoms of the nitrogen-containing ring; Alkylene-bis-isoquinolines with hydrocarbon or substituted hydrocarbon radicals attached to the ring nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/18—Aralkyl radicals
- C07D217/20—Aralkyl radicals with oxygen atoms directly attached to the aromatic ring of said aralkyl radical, e.g. papaverine
Definitions
- 1-benzyl-Z-alkyl-octahydroisoquinolines of the general Formula VI may be prepared by condensing ,B-cyclohexene-(l)-yl-ethylamine (I) with substituted or unsubstituted phenyl-acetic acids, cyclizing the resulting acid amides with dehydrating agents so as to obtain the corresponding l-benzyl-3,4,5,6,7,S-hexahydroisoquinolines and hydrogenating the latter to the octahydro compounds.
- v.octahydroisoquinolines of the general Formula VI and their salts can be obtained by reacting a phenyl-acetylhalide of the formula CHzC OX formulae scheme:
- the compounds of the general Formula VI are therefore formed by hydrogenation of a CC-double bond.
- the products of the present process may be used as intermediates for the manufacture of N-alkylmorphinanes.
- Example 1 600 parts by weight of methyl-formate are slowly dropped into 125.2 parts by Weight of cooled fi-cyclohexene (1) yl ethylamine. After the initially rather strong reaction has subdued, the mixture is boiled for an hour.
- LiAlH4 45.5 parts by Weight of LiAlH4 are suspended in 2000 parts by volume of absolute ether under nitrogen and jclohexene-(1')-yl-ethane distilled in the vacuum of a water-jet pump; boiling point -90 C. (15 mm.); melting point of the hydrochloride -142 C. (from isopropyl alcohol).
- the phenyl-acetic-N-[cyclohexene-(1)-ylethylJ-N-methyl-amide remains behind as a light-yellow viscous oil which is distillable but also directly employable for further use.
- the remaining 1-benzylidene-2- methyl-1,2,3,4,5,6,7,S-octahydroisoquinoline is dissolved in ten times the quantity of methanol and hydrogenated in the presence of 60 parts by weight of Raney nickel at room temperature and normal pressure. After the quantity of hydrogen calculated for 1 mol has been taken up, the hydrogenation is stopped and the catalyst filtered off. The residue remaining behind after the evaporation of the methanol represents the 1-benzyl-2-methyl- 1,2,3,4,5,6,7,8-octahydroisoquinoline, the hydrochloride of which melts at 195-196 C.
- Example 2 A solution of 185 parts by weight of p-methoxyphenyl-acetyl-chloride in 450 parts by volume of absolute benzene is slowly added, with ice-cooling and stirring, to 278 parts by Weight of l-methyl-amino-2-cyclohexene- (1')-yl-ethane in 1400 parts by volume of absolute benzene. The reaction product is then allowed to stand for one hour at room temperature and subsequently heated on a water-bath for minutes.
- octahydroisoquinoline is dissolved in ten times the quantity of methanol and hydrogenated in the presence of 60 parts by weight of Raney nickel. After working up, the 1 (p methoxybenzyl) 2 methyl 1,2,3,4,5,6,7,8-
- octahydroisoquinoline remains behind in the form of an oil which boils at 120 C. at a pressure of 0.01 mm.; melting point of the oxalate 163-164 C. (from alcoholether).
- Example 3 230 parts by Weight of phosphorus pentachloride are slowly added to a suspension of 196.2 parts by weight of homoveratric acid in 2000 parts by volume of absolute benzene. After the initially lively reaction has come .to a standstill, the mixture is heated for 15 minutes to N-alkyl wherein R and R are selected from the group consisting of hydrogen and hydroxy, methoxy, acetoxy, benzyloxy and carbethoxyoxy radicals.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
PROCESC FOR THE MANUFACTURE OF OCTAHY- DROISOQUINOLINE DERIVATIVES'AND INTER- MEDIATES THEREIN Joseph Hellerbach, Basel, Switzerland, assignor to Hottmann-La Roche Inc., Nutley, N. .L, a corporation of New Jersey No Drawing. Application November 15, 1951, Serial No. 256,623
Claims priority, application Switzerland January 16, 1951 5 Claims. (Cl. 260-240) It is known (0. Schnider and I. Hellerbach, Helvetica Chimica Acta, volume 33, year 1950, page 1437) that 1-benzyl-Z-alkyl-octahydroisoquinolines of the general Formula VI may be prepared by condensing ,B-cyclohexene-(l)-yl-ethylamine (I) with substituted or unsubstituted phenyl-acetic acids, cyclizing the resulting acid amides with dehydrating agents so as to obtain the corresponding l-benzyl-3,4,5,6,7,S-hexahydroisoquinolines and hydrogenating the latter to the octahydro compounds.
.The subsequent N-alkylation then yields the l-benzyl-Z- alkyl-1,2,3,4,5,6,7,8-octahydroisoquinolines substituted or unsubstituted in the aromatic ring.
It has now been found, according to the present invention, that the same l-benzyl-Z-alkyl-1,2,3,4,5,6,7,8-
v.octahydroisoquinolines of the general Formula VI and their salts can be obtained by reacting a phenyl-acetylhalide of the formula CHzC OX formulae scheme:
NH-alkyl N-alkyl 0o R III IV Z ,7 l 9 ,150 Patented Sept. 27, 1955 ice N-alkyl N-alkyl H CH2 I 1 V VI The l-alkylamino-Z-cycldhexene-(1')-yl-ethanes III required as starting materials can, for instance, be obtained by acylation of fl-cyclohexene-(l)-yl-ethylamine and subsequent reduction. By reaction with unsubstitutedor substituted phenyl-acetyl-halides the secondary amines III are converted into the corresponding phenylacetic N [cyclohexene (1) yl ethyl] N alkyl amides IV. By treatment with dehydrating agents such as POCls or P205, the latter compounds are allowed to be cyclized to the unsubstituted or substituted l-benzylidene-2-alkyl-l,2,3,4,5,6,7,8-octahydroisoquinolines which, when hydrogenated, furnish the corresponding benzyl compounds.
The new synthesis difiers in principle from the known method in that the isoquinoline compound V is obtained under formation of a semicyclic double bond. The compounds of the general Formula VI are therefore formed by hydrogenation of a CC-double bond.
The products of the present process may be used as intermediates for the manufacture of N-alkylmorphinanes.
Example 1 600 parts by weight of methyl-formate are slowly dropped into 125.2 parts by Weight of cooled fi-cyclohexene (1) yl ethylamine. After the initially rather strong reaction has subdued, the mixture is boiled for an hour.
Excess methyl-forrnate is evaporated and the remaining 1-formylamino-2-cyclohexene-(1')yl-ethane distilled in the vacuum of a water-jet pump at 168-171" C. (13 mm.).
45.5 parts by Weight of LiAlH4 are suspended in 2000 parts by volume of absolute ether under nitrogen and jclohexene-(1')-yl-ethane distilled in the vacuum of a water-jet pump; boiling point -90 C. (15 mm.); melting point of the hydrochloride -142 C. (from isopropyl alcohol).
154.6 parts by weight of phenyl-acetic chloride in 450 parts by volume of absolute benzene are dropped at 0 C. intoa well-stirred solution of 278.5 parts by weight -of 1-methy1amino-2-cyclohexene-(1')-yl-ethane in 1400 a parts by volume of absolute benzene and allowed to stand for 3 hours at room temperature. The condensation product is successively washed with 3 N hydrochloric acid, water, 3 N soda and water. After distilling off the solvent, the phenyl-acetic-N-[cyclohexene-(1)-ylethylJ-N-methyl-amide remains behind as a light-yellow viscous oil which is distillable but also directly employable for further use.
257.3 parts by weight of phenyl-acetic-N-[cyclohexene- (1)-yl-ethyl]-N-methyl-amide are heated with 300.6 parts by weight of phosphorus oxychloride in 1300 parts by volume of absolute benzene for 2 hours at 95 C. and subsequently poured into water. After addition of ether, the phosphoric acid salts are brought into aqueous solution by shaking and the latter repeatedly washed with ether. Concentrated NaOH is then added cautiously to the ice-cold aqueous solution, and the separated base taken up in ether which, after washing with water, is dried and distilled off. The remaining 1-benzylidene-2- methyl-1,2,3,4,5,6,7,S-octahydroisoquinoline is dissolved in ten times the quantity of methanol and hydrogenated in the presence of 60 parts by weight of Raney nickel at room temperature and normal pressure. After the quantity of hydrogen calculated for 1 mol has been taken up, the hydrogenation is stopped and the catalyst filtered off. The residue remaining behind after the evaporation of the methanol represents the 1-benzyl-2-methyl- 1,2,3,4,5,6,7,8-octahydroisoquinoline, the hydrochloride of which melts at 195-196 C.
Example 2 A solution of 185 parts by weight of p-methoxyphenyl-acetyl-chloride in 450 parts by volume of absolute benzene is slowly added, with ice-cooling and stirring, to 278 parts by Weight of l-methyl-amino-2-cyclohexene- (1')-yl-ethane in 1400 parts by volume of absolute benzene. The reaction product is then allowed to stand for one hour at room temperature and subsequently heated on a water-bath for minutes. When working up according to Example 1, the p-methoxy-phenyl-acetic- N-(cyclohexenyl-ethyl)-N-methyl-amide is obtained as an oil of light-yellow colouring which can be used without further purification.
287.4 parts by weight of p-methoxy-phenyl-acetic-N- [cyclohexene-(1)-yl-ethyl]-N-methyl-amide are heated with 306 parts by weight of POCl in 1500 parts by volume of benzene for 2 hours at 95 C. The reaction product is then worked up in an analogous manner as described in Example 1. The remaining viscous l-(pmethoxy benzylidene) 2 methyl 1,2,3,4,5,6,7,8-
octahydroisoquinoline is dissolved in ten times the quantity of methanol and hydrogenated in the presence of 60 parts by weight of Raney nickel. After working up, the 1 (p methoxybenzyl) 2 methyl 1,2,3,4,5,6,7,8-
octahydroisoquinoline remains behind in the form of an oil which boils at 120 C. at a pressure of 0.01 mm.; melting point of the oxalate 163-164 C. (from alcoholether).
Example 3 230 parts by Weight of phosphorus pentachloride are slowly added to a suspension of 196.2 parts by weight of homoveratric acid in 2000 parts by volume of absolute benzene. After the initially lively reaction has come .to a standstill, the mixture is heated for 15 minutes to N-alkyl wherein R and R are selected from the group consisting of hydrogen and hydroxy, methoxy, acetoxy, benzyloxy and carbethoxyoxy radicals.
2. A process of producing a l-benzylidene-Z-alkyl- 1,2,3,4,5,6,7,8-octahydroisoquinoline represented by the formula @qvalkyl I l C I wherein R and R are each selected from the group consisting of hydrogen, hydroxy, methoxy, acetoxy, benzyloxy, and carbethoxyoxy radicals, which comprises treating a phenyl-acetic-N- [cyclohexene-( 1)-yl-ethyl]-N- alkyl-amide represented by the formula N-alkyl 0 o wherein R and R are each selected from the group consisting of hydrogen, hydroxy, methoxy, acetoxy, benzyloxy, and carbethoxyoxy radicals, with a cyclicizingdehydrating agent of the class consisting of phosphorus oxides and phosphorus oxyhalides.
3. 1-benzylidene-2-methyl-1,2,3,4,5,6,7,8-octahydroisoquinoline.
4. l-(p-methoxy-benzylidene)-2-methyl-l,2,3,4,5,6,7,8- octahydroisoquinoline.
5. 1 (3,4' dimethoxy benzylidene) 2 methyl- 1,2,3,4,5,6,7,8-octahydroisoquinoline.
References Cited in the file of this patent UNITED STATES PATENTS Schuloff Dec. 20, 1927 Middleton Sept. 9, 1941 Riester Jan. 11, 1944 Argyle Nov. 13, 1945 10 OTHER REFERENCES Clarke et aL, The Chemistry of Penicillin (Princeton University Press, Princeton, N. J., 1949), pp. 660-664.
Grewe, Chem. Ber., p. 281 (1948).
Schnider et al., Helv. Chim Acta, vol. 33, p. 1447.
Claims (1)
1. 1-BENZYLIDENE-2-ALKYL-1,2,3,4,5,6,7,8-OCTAHYDROISO QUINOLINE OF THE GENERAL FORMULA
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH2719150X | 1951-01-16 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| US2719150A true US2719150A (en) | 1955-09-27 |
Family
ID=4571298
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| US256623A Expired - Lifetime US2719150A (en) | 1951-01-16 | 1951-11-15 | Process for the manufacture of octahydroisoquinoline derivatives and intermediates therein |
Country Status (1)
| Country | Link |
|---|---|
| US (1) | US2719150A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3149104A (en) * | 1961-01-03 | 1964-09-15 | Sterling Drug Inc | 4-hydroxy-7-styryl-1, 8-naphthyridine-3-carboxylic acids and esters |
| US3337539A (en) * | 1962-10-10 | 1967-08-22 | Chinoin Gyogyszer Es Vegyeszet | Tetraethoxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives and salts thereof |
Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1653314A (en) * | 1925-12-11 | 1927-12-20 | Ig Farbenindustrie Ag | Bodies of desensitizing action and process of making same |
| US2255077A (en) * | 1938-03-21 | 1941-09-09 | Du Pont Film Mfg Corp | Filter dyes for color photography |
| US2338782A (en) * | 1940-07-30 | 1944-01-11 | Riester Oskar | Cyanine dyestuff |
| US2388663A (en) * | 1941-12-05 | 1945-11-13 | British Celanese | Aroylaminonitrodiphenylamine |
| US2463942A (en) * | 1945-08-24 | 1949-03-08 | Lilly Co Eli | N-phenylacetylated amino alcohols and ethers |
| US2554842A (en) * | 1947-09-13 | 1951-05-29 | Hoffmann La Roche | Octahydroisoquinoline derivatives |
| US2634272A (en) * | 1950-05-27 | 1953-04-07 | Hoffmann La Roche | 1-benzyl-hexahydroisoquinolines and preparation thereof |
-
1951
- 1951-11-15 US US256623A patent/US2719150A/en not_active Expired - Lifetime
Patent Citations (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US1653314A (en) * | 1925-12-11 | 1927-12-20 | Ig Farbenindustrie Ag | Bodies of desensitizing action and process of making same |
| US2255077A (en) * | 1938-03-21 | 1941-09-09 | Du Pont Film Mfg Corp | Filter dyes for color photography |
| US2338782A (en) * | 1940-07-30 | 1944-01-11 | Riester Oskar | Cyanine dyestuff |
| US2388663A (en) * | 1941-12-05 | 1945-11-13 | British Celanese | Aroylaminonitrodiphenylamine |
| US2463942A (en) * | 1945-08-24 | 1949-03-08 | Lilly Co Eli | N-phenylacetylated amino alcohols and ethers |
| US2554842A (en) * | 1947-09-13 | 1951-05-29 | Hoffmann La Roche | Octahydroisoquinoline derivatives |
| US2634272A (en) * | 1950-05-27 | 1953-04-07 | Hoffmann La Roche | 1-benzyl-hexahydroisoquinolines and preparation thereof |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3149104A (en) * | 1961-01-03 | 1964-09-15 | Sterling Drug Inc | 4-hydroxy-7-styryl-1, 8-naphthyridine-3-carboxylic acids and esters |
| US3337539A (en) * | 1962-10-10 | 1967-08-22 | Chinoin Gyogyszer Es Vegyeszet | Tetraethoxy-1, 2, 3, 4-tetrahydroisoquinoline derivatives and salts thereof |
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